In mammalian cells, intercellular junctions are typically categorized into four types, based on early electron microscope studies: adherens junctions, desmosomes, gap junctions, and tight junctions. Recent research interest has focused on the molecular organization and functions of these junctions, to not only explain cell-cell interactions and communication within multi-cellular organisms, but also to regulate paracellular permeability for therapeutic purposes.
Drug absorption across epithelial and endothelial tissue is limited in several stages. One important barrier is created by intercellular tight junctions which limit movement of substances between cells (Anderson, J. M., and Van Itallie, C. M., Am. J. Physiol. (GI and Liver) 269:G467-G475 (1995)). The tight junction barrier appears to be created by extracellular contacts of a transmembrane protein called occludin. The protein was originally cloned from the chicken (Furuse, M., et al., J. Cell Biol. 123: 1777-1788 (1993)). Occludin has subsequently been cloned and sequenced from human, mouse, dog and rat kangaroo (Ando-Akatsuka, Y., et al., J Cell Biology 133: 43-47 (1996). Human occludin has also been cloned and sequenced by applicants (Genbank Accession U53823; see SEQ ID NOs 1 and 2 and FIG. 1).
Tight junctions create a regulated paracellular barrier to the movement of water, solutes, macromolecules, immune cells, and the like between and among both epithelial and endothelial cells. New evidence has elucidated information about proteins involved in this dynamic regulation.
It would be beneficial to utilize this information to alter paracellular permeability for specific medical purposes.